High Blood Press Cardiovasc Prev

https://doi.org/10.1007/s40292-018-0261-4

REVIEW ARTICLE

Therapeutic Approach to Hypertension Urgencies

and Emergencies in the Emergency Room
Alessandro Maloberti1,2 • Giulio Cassano1 • Nicolò Capsoni1 • Silvia Gheda1 •
Gloria Magni1 • Giulia Maria Azin1 • Massimo Zacchino1 • Adriano Rossi1 •
Carlo Campanella1 • Andrea Luigi Roberto Beretta3 • Andrea Bellone3 •
Cristina Giannattasio1,2

Received: 9 February 2018 / Accepted: 5 May 2018

Ó Springer International Publishing AG, part of Springer Nature 2018

Abstract Hypertensive urgencies-emergencies are impor- Keywords Hypertensive urgencies
Hypertensive

tant and common events. They are defined as a severe
elevation in BP, higher than 180/120 mmHg, associated or
not with the evidence of new or worsening organ damage
for emergencies and urgencies respectively. Anamnestic
information, physical examination and instrumental eval-
uation determine the following management that could
need oral (for urgencies) or intravenous (for emergencies)
anti-hypertensives drugs. The choice of the specific drugs
depend on the underlying causes of the crisis, patient’s
demographics, cardiovascular risk and comorbidities. For
emergencies a maximum BP reduction of 20–25% within
the first hour and then to 160/110–100 over next 2–6 h, is
considered appropriate with a further gradual decrease over
the next 24–48 h to reach normal BP levels. In the case of
hypertensive urgencies, a gradual lowering of BP over
24–48 h with an oral medication is the best approach and
an aggressive BP lowering should be avoided. Subsequent
management with particular attention on chronic BP values
control is important as the right treatment of the acute
phase.
This article is part of the topical collection on Hypertension Urgencies
& Emergencies.
& Cristina Giannattasio
cristina.giannattasio@unimib.it;
cristina.giannattasio@ospedaleniguarda.it
1
School of Medicine and Surgery, University of Milano-
Bicocca, Milan, Italy
2
Cardiologia IV, Dipartimento A. De Gasperis, Ospedale
Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20159
Milan, Italy
3
Emergency Department, Niguarda Ca Granda Hospital,
Milan, Italy
emergencies
Therapeutic approach
Emergency
department
1 Introduction
Hypertensive urgencies-emergencies are important and
common events that need to be well known among who
work in the emergency department. Even though clinical
and therapeutic approach to chronic hypertension is well
codified by international guidelines, there are few evidence
based recommendations for the management of an acute
and severe elevation of blood pressure (BP) [1–3].
According to the 2017 American College of Cardiology
(ACC) guidelines these events should be classified as
emergency or urgency. The first group is defined as a
severe elevation in BP, higher than 180/120 mmHg, asso-
ciated with evidence of new or worsening organ damage
[1]. Acute organ damage associated with hypertensive
emergencies include cardiac (acute myocardial infarction,
acute left ventricular failure with pulmonary edema,
unstable angina pectoris, aortic dissection), neurological
(hypertensive encephalopathy, acute ischemic or haemor-
rhagic stroke) and others organs (acute renal failure and
haemolytic microangiopatic anemia) involvement [4, 5]. In
contrast hypertensive urgencies are defined as severe ele-
vation in BP without acute organ damage [1].
This review will discuss the management of hyperten-
sive urgencies and emergencies in the emergency depart-
ment dealing with the initial assessment, focusing on drug
treatment and finishing with a brief section of outcome and
subsequent management.

2 Initial Assessment
Anamnestic information, physical examination and instru-
mental evaluation determine the following management of
acutely elevated BP values. An early and rapid assessment
is critical to limit morbidity and mortality in hypertensive
emergencies.
The medical history should include details about eval-
uation of pre-existing hypertension’s duration and severity,
presence of previous end-organ damage (cardiovascular
and renal one), antihypertensive therapy, intake of over-
the-counter preparation (i.e. sympathomimetics agents) and
illicit drugs.
BP should be measured according to standard technique
both in supine and in standing position and in both arms
with the presence of a significant difference that lead to the
high suspect of aortic dissection.
Physical examination should be focused on the exclu-
sion of signs of end-organ damage and so jugular venous
distension, crackles or rales, third heart sound, level of
consciousness, presence of focal neurological signs, visual
fields and signs of meningeal irritation.
Blood exams should include complete blood count,
serum creatinine and concentration of urea. Further nec-
essary evaluation are electrocardiogram, chest X-ray while
uranalysis, fundoscopy, troponin dosage, cardiac and/or
abdominal ultrasound and brain computed tomography
should be performed depending on the physical examina-
tion and the results of previous exams. Those recom-
mended test are completely done only in the 6% of patient
admitted in emergency department for hypertensive
urgencies-emergencies with the most complete evaluation
in the case of cardiovascular presentation symptoms [6].
3 Treatment
Evidences from Randomized Clinical Trials (RCTs) and
guidelines about management of hypertensive crises are
lacking. Rate and time interval for BP reduction and the
drug choice are based only on experts’ opinion and retro-
spective studies [7].
The distinction between hypertensive urgencies and
emergencies is crucial to drive clinical approach. In fact, in
patients presenting with hypertensive emergencies prompt
diagnosis and treatment are decisive to prevent progression
of acute organ damage and reduce morbidity and mortality
[7]. A short acting and titratable parenteral drug is pre-
ferred in a setting where a close monitoring of BP could be
performed whereas other routes (as intramuscular or sub-
lingual) should be avoided for their
unpredictable pharmacokinetics.
A. Maloberti et al.
Because of altered autoregulation of BP in hypertensive
emergency, a rapid decline could lead to impaired tissue
perfusion and subsequent organ ischemia, and it should be
avoided [8]. Even if the optimal time and rate of BP
reduction are not well known, a maximum BP reduction of
20–25% within the first hour and then to 160/110–100 over
next 2–6 h, is considered appropriate [1, 8].
Two exceptions are represented by cerebrovascular
accidents and acute aortic dissection. In the former, a less
aggressive reduction is recommended to preserve brain
perfusion while, in the latter, BP and heart rate reduction
should be more aggressive to reduce shear forces on arte-
rial wall [8, 9].
After the first reduction, in the absence of a progression
of organ damage, a further gradual decrease over the next
24–48 h to reach normal BP levels should be attempted
[8, 10]. Once BP has reached target values, a slow down-
titration of parenteral drugs can be performed with initia-
tion of an oral agent [8].
To date, limited data on the efficacy and safety of dif-
ferent classes of antihypertensive agents (both parenteral
and oral) has been reported. A Cochrane review published
in 2008, shows that RCT’s evidence of the impact on
mortality and morbidity of drug treatment in hypertensive
urgencies-emergencies is insufficient. No single class agent
results more effective than others in improving patients’
outcome while only minor differences in degree of BP
lowering has been found [1].
On the contrary, in the case of hypertensive urgencies, a
gradual lowering of BP over 24–48 h with an oral medi-
cation is the best approach and an aggressive BP lowering
should be avoided [1]. In fact, hypertensive urgencies are
frequently a manifestation of uncontrolled chronic hyper-
tension. As previously cited, most of these patients have a
rightward shift of pressure/flow autoregulation curve of
cerebral, myocardial and renal arterial microcirculation, so
that a rapid correction of severely elevated BP below the
autoregulatory range can cause an excessive reduction in
tissue perfusion, till organ ischemia and infarction.
For both urgencies and emergencies when the clinician
choose the antihypertensive agent should consider the
underlying causes of the crisis, patient’s demographics,
cardiovascular risk and comorbidities.
Tables 1 and 2 reports the most commonly used oral and
parental drugs (for urgencies and emergencies respec-
tively) with their onset and duration of action as well as
principal indications and contraindications. Italian avail-
able formulation and standard dilution protocol used by our
institution has been used for parental drugs indications.
Finally Table 3 summarized the different hypertensive
emergencies with the preferred medications and specific
indications.
Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room

Table 1 Oral agents for hypertensive urgencies

Drug Dose Onset Duration Contraindications Adverse effect

Captopril 12,5–25 mg, 15–30 min 4–6 h Renal arteries stenosis, severe Acute renal failure, hypotension, orthostatic
repeatable after aortic valve stenosis, marked syncope
30–60 min hypovolemia, pregnancy
Nifedipine 5–10 mg, 5–30 min 6h Elderly patients, History of Abrupt hypotension with reflex tachycardia,
fast- repeatable after vasculopathy, angina myocardial infarction, cerebrovascular accident,
acting 30–60 min acute renale failure, flashing, headache syncope
Nifedipine 20 mg 4–5 h 10–12 h None absolute Palpitation, flushing and peripheral edema
extended
release
Amlodipine 5–10 mg 4–6 h At least None absolute Palpitation, flushing and peripheral edema
24 h

4 Oral Treatment for Hypertensive Urgencies administration of a fast-acting nifedipine capsule

4.1 Captopril
Captopril is an Angiotensin-Converting Enzyme Inhibitor
(ACE-I) frequently used in the management of hyperten-
sive urgencies-emergencies both orally and sublingually.
When administered orally it has an onset time variable
between 15 and 30 min and an action lasting 4–6 h. The
sublingual route decrease BP more efficiently in the first 10
and 30 min, with an equalization of difference at 60 min
[11]. Oral usage is therefore considered preferable because
safer and more agreeable at the same time (bad taste and
local mucosal trauma reported with sublingual usage)
whereas the sublingual method remains useful in patients
unable to swallow. The recommended dosage is
12.5–25 mg repeatable after 30–60 min [12, 13]. The main
side effects are hypotension, acute renal failure and
angioedema. Contraindications are represented by renal
artery stenosis, severe aortic stenosis, severe hypovolemia
and pregnancy (due to its teratogenic effects).
Compared to nifedipine 10 mg, captopril 25 mg has
been shown to be equally effective in terms of blood
pressure reduction, but with fewer side effects [11, 14, 15].
An exception is represented by black patients in which
nifedipine is reported to be more potent, as it is in general
for Calcium Channel Blockers (CCB) in comparison with
ACE-I in those subjects [16].
4.2 Nifedipine
Nifedipine is an oral/sublingual dihydropyridine CCB
widely used for hypertensive urgencies-emergencies.
Nifedipine’s oral mucosal absorption is actually negligible
whereas it is rapidly absorbed from the GI tract; therefore,
the efficacy linked to the sublingual route is probably due
to the contemporary GI absorption [17]. After
(5–10 mg) a rapid decrease in BP is usually observed in
5–10 min and a peak effect in 30–60 min whereas the
duration of action ranges between 6 and 8 h [8]. The effect
is unpredictable and may be excessive, resulting in
hypotension and reflex tachycardia with complaints of
flushing, headache, palpitation, and nausea. Furthermore,
cerebral, renal, and myocardial ischemic events precipi-
tated by nifedipine have been reported, with elderly
hypertensive patients with an underlying vasculopathy and
organ impairment being the most vulnerable. For these
reasons and for the lack of any clinical documentation of its
benefit, fast-acting sublingual and oral nifedipine capsule
usage is not advised in the management of hypertensive
urgencies-emergencies [8]. Nifedipine retard, 20 mg
orally, appears to have a safer and more effective profile.
This slow-release preparation lowers BP 15–30 min after
intake with a maximal effect after 4–6 h and produce a
long-lasting plasma levels of the drug with a prolonged
reduction of BP until 10–12 h. Avoiding an abrupt droop in
BP which could be harmful, nifedipine retard has a good
time of action and decreases BP more gradually, smoothly
and for longer time [9, 16]. Considering timing of BP
reduction aimed in the management of hypertensive
urgencies, it represents a valid option.
4.3 Amlodipine
Amlodipine is an oral dihydropyridine CCB. It has a good
GI absorption with a peak concentration at 6–12 h after
intake. Significant reductions in blood pressure is usually
reached after 24–48 h after the first dose; reflex slight
increase in heart rate usually appears after 10 h following
vasodilatation. Side effects are represented by palpitation,
flushing and peripheral edema. In some cases in which
captopril or nifedipine will not be available it could
Table 2 Parenteral agents for hypertensive emergencies
Drug Italian Possible Dose Onset Duration Role Contraindication Adverse effect
available dilution
formulation

Labetalol 100 mg/ 2 fl in Bolus: 20 mg bolus; repeat 5–10 min 3–6 h Myocardial ischemia, Bronchial asthma, Bradycardia, conduction
20 mL 200 mL of boluses of 20–80 mg hyperadrenergic states, overt cardiac failure, disturbances,
(5 mg/mL) standard every 10 min; aortic dissection, greater than first bronchospasm, nausea,
Trandate solution Continuous infusion: encephalopathy, degree heart block, vomiting, dizziness, scalp
(1 mg/mL) starting from 1–2 mg/ preeclampsia cardiogenic shock, tingling, orthostatic
min; max total day severe bradycardia hypotension
dosage of 300 mg
Esmolol 100 mg/ bolus: 1 fl in 250–500 mcg/kg/min in 1–5 min 15–30 min Myocardia, ischemia, 2nd and 3rd ° AV Bradycardia, heart
10 mL 20 mL of bolus followed by hyperadrenergic states, block, cardiogenic conduction disturbances,
(10 mg/mL) standard or 50–100 mcg/kg/min in aortic dissection, shock, CHF, bronchospasm, nausea,
5% infusion; repeat bolus encephalopathy, concomitant IV hypotension, heart failure
Brevibloc
glucose after 5 min if needed or perioperative calcium channel
solution increase infusion to 300 blockers Pregnancy
(5 mg/mL) mcg/kg/min (2nd and 3rd
Infusion:4 fl trimester)
in 50 mL
of standard
or 5%
glucose
solution
(8 mg/mL)
Nicardipine 25 mg/ 1 fl in 5 mg/h increase by 2.5 mg 5–10 min 15–30 min, Aortic dissection in Tachyphylaxis, avoid Headache, flushing, nausea,
10 mL 250 mL of increments every 20 min may last conjunction with beta calcium channel reflex tachycardia, edema,
standard or to a max of dose of several blocker, cardiac blockers in CHF local phlebitis
5% 15 mg/h hours ischemia, stroke, CNS Caution of coronary
glucose bleed, hyperadrenergic steal with cardiac
solution conditions, ischemia
(0.1 mg/ encephalopathy, renal
mL) failure
Clevidipine 25 ml/50 ml No dilution 1–2 mg/h doubled every 2–4 min 5–20 min Conjunction with beta Egg or soy allergy Headache, flushing, nausea,
or 50 mg/ 90 s to a max of 16 mg/h blocker, CHF, cardiac vomiting, reflex
100 mL ischemia, stroke, CNS tachycardia, hypotension,
bleed, hyperadrenergic rebound hypertension
(0,5 mg/mL)
conditions,
Cleviprex encephalopathy, renal
failure
Postoperative
hypertension
A. Maloberti et al.
Table 2 continued
Drug Italian Possible Dose Onset Duration Role Contraindication Adverse effect
available dilution
formulation

Fenoldopam 20 mg/2 ml 20 mg in 0.1–0.6 mcg/kg/min titrate 5–10 min 15–30 min Renal failure, aortic Glaucoma Hypotension, headache,
or 100 mL every 15 min to a max dissection (in tachycardia, nausea,
50 mg/5 mL (0,2 mg/mL dose of 0.6 mcg/kg/min conjunction with beta flushing
blocker)
Corlopam
Sodium 100 mg 1 fl in 0.25 mcgg/kg/min to max Seconds 1–2 min Aortic dissection (in Avoid in Nausea, vomiting,
nitroprusside 250 mL of of 2 mcg/kg/min after conjunction with beta- cerebrovascular thiocyanate and cyanide
5% stopping blocker), events. Caution in toxicity, increased
glucose hyperadrenergic renal insufficiency— intracranial pressure,
solution conditions, rates [ 4 mcg/kg/ decreased cerebral blood
(0.4 mg/ encephalopathy min can cause toxic flow, coronary steal,
mL) levels of cyanate muscle twitching, sweats
Nitroglycerin 5 mg/1,5 mL 1 fl in 5 mcg/min titrate by 5 mcg/ 2–5 min 5–10 min Cardiac ischemia, Concurrent use PDE-5 Methemoglobinemia,
Venitrin 250 mL of min every 15 min to a congestive heart failure, inhibitors, headache, dizziness,
standard max dose of 100 mcg/ hyperadrenergic states, tachyphylaxis, vomiting
solution min encephalopathy, renal caution in right
or 2 fl in failure ventricular infarct
500 mL of
standard
solution
(0,02 mg/
mL)
Hydralazine 10–20 mg bolus q30 min 10–20 min 1–4 h IV Eclampsia; caution given Reflex tachycardia
until target BP reached IV 4–6 h IM erratic response
10–40 mg IM 20–30 min
Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room

IM
Furosemide 20 mg/2 mL 20–40 mg bolus, repeat 5 min 2h Volume overload; Hyponatremia,
250 mg/ q2 h pulmonary oedema hypokalemia,
25 mL Continuous infusion: max hypochloremic alkalosis,
4 mg/min dehydratation
Urapidil 50 mg/ 4 fl in 12.5–50 mg bolus; a 5–10 min 2–7 h Aortic isthmus stenosis Dizziness, nausea and
10 mL 500 mL F second 50 mg bolus can or arteriovenous headache
Ebrantil o G5% be administered if no shunt (excluding
(0,4 mg/ effect is observed within haemodynamic non-
mL) 5 min effective dialysis
Alternatively, continuous shunt) and lactation
infusion: initial rate
2 mg/min; maintenance
9 mg/h
 A. Maloberti et al.

represent a fair treatment option for hypertensive urgen-

cies-emergencies [18].

atrioventricular block,

Reflex tachycardia,
headache, nausea
Adverse effect

Hypotension
Bradycardia, 5 Parental Treatment for Hypertensive
Emergencies

Ischemic heart disease 5.1 Labetalol

Labetalol is a combined selective alpha-1 and nonselective

renal insufficiency
events. Caution in

beta-adrenergic receptor blocker with an alpha-to-beta

cerebrovascular
Contraindication

blocking ratio of 1–7. Labetalol is metabolized by the liver

to form an inactive glucuronide conjugate with an elimi-
Avoid in

nation half-life of about 5.5 h [19]. The hypotensive effect

of intravenous labetalol begins within 2–5 min after
administration, reaching a peak at 5–15 min, and lasting
for about 2–6 h. Because of its beta-blocking effects, the
Pheochromocytoma and
other catecholamine
Clonidine withdrawal

heart rate is either maintained or slightly reduced and,

unlike pure beta-adrenergic blocking agents, labetalol
excess states

doesn’t affect cardiac output. It act reducing the systemic

vascular resistance without reducing total peripheral blood
flow and so maintaining cerebral, renal and coronary blood
Role

flow [20, 21]. For this reason it is one of the preferred

choice for acute myocardial ischemia, aortic dissection,
acute ischemic stroke and hypertensive encephalopathy.
5–10 min
Duration

Furthermore it is widely used in the setting of pregnancy-

13 h

induced hypertensive emergencies (pre-eclampsia and

eclampsia) as little placental transfer occurs, mainly
because of negligible lipid solubility.
1–2 min
10 min

Labetalol may be given as loading dose of 20 mg, fol-

Onset

lowed by repeated incremental doses of 20–80 mg given at

10 min intervals until the desired BP is achieved. Alter-
5–10 mg repeat q5–15 min
or drip at 0.2–5 mg/min

natively, after the initial loading dose, it may be infused

starting at 1–2 mg/min and titrated up until the desired
hypotensive effect is achieved. Bolus injections of 1–2 mg/
kg have been reported to produce precipitous falls in BP
150–300 mcg

and should therefore be avoided.

slow bolus
Dose

5.2 Esmolol
bolus: 1 fl in

This is a very short-acting beta-blocker with a onset of

10 mL F

action within 60 s and a duration of 10–20 min [8, 19].

Possible
dilution

Esmolol metabolizes via rapid hydrolysis of ester linkages

by red blood cell esterases and is not dependent upon renal
or hepatic function. Because of its pharmacokinetic prop-
disponibile
10 mg/1 mL

capito se è
formulation

Catapresan

in italia)

erties, some authors consider it an ‘ideal beta-adrenergic

150 mcg/
available

(non ho
Regitin
1 mL

blocker’ for use in critically ill patients. On the contrary of

Italian

labetalol it decreases heart rate, myocardial contractility

Table 2 continued

and cardiac output and so it’s a suitable agent in situations

Phentolamine

in which those parameter are increased together with BP

Clonidine

values. It has proven to be well tolerated in patients with

acute myocardial infarction, even those who have relative
Drug

contraindications to beta-blockers. Typically, the drug is

Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room

Table 3 Preferred medications and specific indications for different hypertensive emergency
Diagnosis Therapeutic goal Suggested therapy Comments

Aortic dissection Reduce shear force on artery wall Labetalol, Esmolol, Nicardipine Measure BP in both arms and threat the
reducing BP and HR: (after b-blocker), Sodium highest one
;SBP \ 140 mmHg nitroprusside Continuous monitoring of BP
;HR \ 60 beats/min Always use b-blocker prior to vasodilator
Vasodilators alone increase wall stress
from reflex tachycardia
Be careful to:
Hypotension (avoid volume depletion)
Respiratory distress in COPD and asthma
patients with b-blocker usage
Cyanide and thiocyanate toxicity in
patients with reduced renal function or
therapy [ 24–48 h
Acute Promote diuresis after vasodilation. Nitroglycerin, nicardipine, Low doses IV Nitrates dilate capacitance
hypertensive Symptoms relief furosemide, sodium nitroprusside vessels; higher doses dilate arterioles
pulmonary ;BP by 20–30% lowering BP
edema Lower survival rates with diuretics alone
(nitrates should be given prior to
diuretics)
Be careful to:
Hypotension
Exacerbation of renal dysfunction
(diuretics and ACE inhibitors)
Acute Reduce ischemia Nitroglycerin sub-lingual or BP [ 185/100 mm Hg is a
myocardial ;MAP no more than 25% intravenous, b-blockers contraindication for thrombolytics
infarction intravenous bolus (metoprolol or Do not give b-blockers in congestive
labetalol) heart failure, low ejection fraction or
other b-blockers contraindications
Do not give nitrates in patients who have
taken phosphodiesterase inhibitors for
ED \ 24 h (\ 48 h for Tadalafil)
Pay attention to vasodilation in right heart
infarction
Acute renal ; BP no more than 25% Nicardipine, fenoldopam, Avoid nitroprusside and ACE-I
failure clevidipine or dialysis Be careful to:
Hypotension
Acute ischemic If thrombolysis candidate treat if Labetalol, nicardipine, sodium Elevated BP spontaneously decrease
stroke BP [ 185/110 mmHg nitoprusside (may be used if BP is within the first few hours after onset of
If thrombolysis excluded treat if not controlled with above drugs acute stroke symptoms
BP [ 220/120 mmHg (after third of or DBP [ 140 mmHg Lowering BP may significantly worsen
three measurements, spaced 15 min ischemia and deficit
apart) Lowering BP by [ 10%–15% in first
24 h should be avoided
Subarachnoid Prevent rebleeding; avoid hypotension to Labetalol, nicardipine, esmolol,
hemorrhage preserve cerebral perfusion (BP cut off clevidipine
not yet defined)
; SBP \ 160 mm Hg or MAP \ 130 mm
 A. Maloberti et al.

Table 3 continued
Diagnosis Therapeutic goal Suggested therapy Comments

Intracranial In patients who present with SBP greater
hemorrhage than 220 mmHg, it is reasonable to use
continuous intravenous drug infusion
and close BP monitoring to lower SBP
Immediate lowering of SBP to less than
140 mm Hg in adults with spontaneous
ICH who present within 6 h of the acute
event and have a SBP between
150 mmHg and 220 mmHg is not of
benefit to reduce death or severe
disability and can be potentially
harmful
Hypertensive ; MAP 20–25% in the first hour
encephalopathy More aggressive lowering may lead to
ischemic infarction
Acute Reduce excessive sympathetic drive.
sympathetic Symptom relief
crisis (cocaine,
amphetamines)
Labetalol, nicardipine, esmolol
Labetalol, nicardipine, fenoldopam,
clevidipine
Benzodiazepine, nitroglycerin,
phentolamine, nicardipine
Early haemorrhage growth often occurs in
first 6 h. During this time, aggressive
BP control may diminish hematoma
growth and so morbidity and mortality
Impairment of cerebral perfusion
autoregulation is possible; avoid rapid
BP lowering
Benzodiazepine are first line agents
(observe for respiratory depression)
b-blockers are not recommended because
unopposed blockade can increase
cocaine toxicity

given as a loading dose of 250–500 mcg/kg over 1–3 min,
followed by an infusion starting at 50 mcg/kg/min and
titrating by 25 mcg/kg/min every 10 mins until 300 mcg/
kg/min. Prior to any dose upward titration, a bolus could be
given because of its extremely short half-life.
5.3 Nicardipine
Nicardipine is a dihydropyridine derivative CCB with
cerebral and coronary vasodilatory activity. The onset of
action of intravenous nicardipine is between 5 and 15 min
with a clinical offset of activity (defined as a 10 mmHg
increase in SBP or DBP after stopping infusion) within
30 min [19]. Nicardipine’s dosage is independent of the
patient’s weight starting with an initial infusion rate of
5 mg/h, increasing by 2.5 mg/h every 5 min (to a maxi-
mum of 15 mg/h) until the desired BP reduction is
achieved [8]. A useful therapeutic benefit of nicardipine is
that the agent has been demonstrated to increase both
stroke volume and coronary blood flow with a favorable
effect on myocardial oxygen balance making it useful for
patients with coronary artery disease and systolic heart
failure [22]. It is also recommended for the treatment of
acute ischemic stroke because of its vasodilatory cerebral
effects.
5.4 Clevidipine
This is a new short-acting intravenous third-generation
dihydropyridine CCB, which is a selective arterial
vasodilator effects available for intraoperative and critical
care settings [23–27].
It is considered unique because of its very short duration
of action (rapid onset and offset). After intravenous infu-
sion of clevidipine butyrate, the arterial blood concentra-
tion declines in a multiphasic pattern. The half-life in the
initial phase is approximately 1 min, and accounts for
about 85–90% of its elimination. The terminal half-life is
approximately 15 min. Clevidipine exhibits extensive
protein binding ([ 99.5%). In a perioperative patient
population, clevidipine produces a 4–5% reduction in
systolic blood pressure within 2–4 min after onset of
infusion. After the infusion is stopped, most patients have
full recovery of blood pressure within 5–15 min. Addi-
tionally, similarly to nicardipine it undergoes metabolism
by plasma esterases and so its elimination is independent of
the liver and kidney and thus there are no restrictions in
patients with hepatic or renal dysfunction. The recom-
mended starting dose of clevidipine is 1–2 mg/h; the dose
is then titrated by doubling at 90-s intervals to a maximum
infusion rate of 16 mg/h.
As it is the last agent approved for this indication, its
safety and efficacy has been reported in a large number of
clinical trials both in the management of postoperative
Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room
hypertension and in hypertensive urgencies-emergencies
[28–30]. A recent open-labeled, single-arm, multicenter
study (VELOCITY) proved its safety and efficacy in a
population of 126 patients presenting to the emergency
department or intensive care unit with an acute elevation in
BP values, 81% of whom had acute end-organ damage
[31]. Within 30 min of starting clevidipine, 89% of patients
achieved target range; the median time to target range was
10.9 min and the mean infusion rate was 5.7 mg/h. The
SBP decreased below the prespecified target range in only
two patients (1.6%) and adverse events include headache,
nausea, atrial fibrillation, chest discomfort, and vomiting.
5.5 Fenoldopam
Fenoldopam is a dopaminergic receptor agonist that act
both as a peripheral vasodilator and as a diuretic. Unlike
other parenteral antihypertensive agents, it maintains or
increases renal perfusion while it lowers blood pressure
[32, 33]. Fenoldopam is less commonly used today; how-
ever, it may be useful in particular situations such as
patients with renal impairment. After starting at 0.1 mcg/
kg/min, the dose can be titrated at 15-min intervals to 0.6
mcg/kg/min, depending upon the blood pressure response.
Fenoldopam should be used cautiously or not at all in
patients with glaucoma due to the possibility of an acute
increase in ocular pressure [32]. In addition, because this
agent is premixed in a solution containing sodium
metabisulfite, caution is recommended for patients with
sulfite sensitivity.
5.6 Sodium Nitroprusside
It is a potent arterial and venous dilator that decreases
preload and afterload. It’s used typically for patients with
acute pulmonary edema and/or severe left ventricular
dysfunction, and in patients with aortic dissection [34].
Continuous intravenous infusion usually starts at 0.25 mcg/
kg/min and can be up titrated to a maximum of 2 mcg/kg/
min. Because of its strong effect on vascular tone it could
increase intracranial pressure leading to decreased cerebral
perfusion, being disadvantageous in patients with hyper-
tensive encephalopathy or a cerebrovascular accident [35].
In patients with coronary artery disease, sodium nitro-
prusside could cause coronary steal which increases the
mortality of patients with acute myocardial infarction [36].
In addition, sodium nitroprusside is associated with clinical
cyanide toxicity even at recommended rates of infusion,
more frequently in patients with renal function reduction.
Regarding this, the molecule of sodium nitroprusside
contains 44% of cyanide that is released non-enzymatically
from nitroprusside. Cyanide is metabolized in the liver to
thiocyanate, which is 100-fold less toxic than cyanide. The
thiocyanate generated is excreted largely through the kid-
neys, therefore, cyanide removal requires adequate liver
function, renal function and bioavailability of thiosulfate
[37]. Cyanide toxicity has been documented to result in
unexplained cardiac arrest, coma, encephalopathy, con-
vulsions and irreversible focal neurological abnormalities.
A rise in serum thiocyanate levels is a late event and not
directly related to cyanide toxicity while red blood cell
cyanide level (although not widely available) may be a
more reliable method of monitoring. A level [ 40 nmol/
mL results in detectable metabolic changes, [ 200 nmol/
mL are associated with severe clinical symptoms and [
400 nmol/mL are considered lethal. Data suggest that
sodium nitroprusside infusion rates [ 4 mcgg/kg/min, for
as little as 2–3 h may lead to cyanide levels in the toxic
range [38]. An infusion of sodium thiosulfate can be used
in affected patients to provide a sulfur donor to detoxify
cyanide into thiocyanate [39].
Risk factors for nitroprusside-induced cyanide poisoning
include a prolonged treatment period ([ 24 to 48 h),
underlying renal impairment, and the use of doses that
exceed the capacity of the body to detoxify cyanide (i.e.,
more than 2 mcg/kg/min). The risk of toxicity can be
minimized by using the lowest possible dose, avoiding
prolonged use (i.e., no more than 2 or 3 days), and by
careful patient monitoring (with special attention to unex-
plained acidemia or decreasing serum bicarbonate
concentrations).
One of the few trial with intravenous antihypertensive
drugs is the ECLIPSE one. Although it regards the
hypertensive management of patients undergoing cardiac
surgery and not the field of hypertensive urgencies-emer-
gencies, in this setting sodium nitroprusside was associated
with a significantly higher perioperative mortality when
compared to clevidipine [28].
5.7 Nitroglycerin
Nitroglycerin is a venodilator that reduces preload and
cardiac output. It is often used in conjunction with other
antihypertensive agents, primarily in acute myocardial
infarction and pulmonary edema. In this setting it is
administered by intravenous infusion and is similar in
action and pharmacokinetics to nitroprusside except that it
produces relatively greater venodilation than arteriolar
dilation. It has less antihypertensive efficacy compared
with other drugs used to treat hypertensive emergencies,
and its effects on blood pressure are very variable in
intensity during the infusion. However, it is very useful in
patients with symptomatic coronary disease and with pul-
monary edema to control symptoms (angina and dyspnea)
and BP values. The initial dose of nitroglycerin is 5 mcg/
min, which can be increased as necessary to a maximum of

100 mcg/min. The onset of action is 2–5 min, while the
duration of action is 5–10 min. Headache (due to direct
vasodilation) and tachycardia (resulting from reflex sym-
pathetic activation) are the primary adverse effects.
Methemoglobinemia has been reported in patients
receiving this agent for more than 24 h. In fact, nitrates are
metabolized in the liver by glutathione reductase to nitrites,
which accelerate oxidation of oxyhaemoglobin to
methaemoglobin. Excessive production may overwhelm
the capacity of the reduction systems and, as inorganic
nitrites are eliminated by the kidneys, renal dysfunction
may predispose to methemoglobinemia.
5.8 Hydralazine
It is a direct-acting arteriolar vasodilator that following IM
or IV administration presents a progressive and often pre-
cipitous fall in BP that can last up to 12 h, often after an
initial latent period of 5–15 min. Although the circulating
half-life of hydralazine is only approximately 3 h, the half-
time of its effect on BP is approximately 10 h [40].
Because of its prolonged and unpredictable antihyperten-
sive effect, it is best avoided in the management of
hypertensive urgencies-emergencies.
5.9 Furosemide
A loop diuretic that blocks NaK2Cl channel in the thick
ascending limb of the Loop of Henle, preventing sodium
and chloride reabsorption. Can be given as an intravenous
bolus or continuous infusion. Volume depletion is common
in patients with hypertensive emergencies and the admin-
istration of a diuretic together with a hypertensive agent
can lead to a precipitous drop in blood pressure. Diuretics
should be avoided unless specifically indicated for volume
overload, as occurs in renal parenchymal disease or coex-
isting pulmonary edema [19].
5.10 Urapidil
This is a new selective alpha-1-adrenergic antagonist that
produces peripheral vasodilatation with no reactive tachy-
cardia because of its antagonism to the serotoninergic
central receptors [41]. Intravenous urapidil reduced preload
(pulmonary capillary wedge pressure and pulmonary artery
pressure) and afterload (systemic vascular resistance)
improving cardiac index and output. It has been widely
used in the prevention and treatment of perioperative high
blood pressure as well as in the hypertensive emergencies
management [42, 43]. This drug may be more suitable for
patients with pre-existing cerebrovascular or cardiovascu-
lar diseases, as the risk of hypoperfusion is rather low in
patients receiving urapidil. Due to a smaller number of
A. Maloberti et al.
adverse events, urapidil is a reasonable alternative to
nitroprusside in the treatment of hypertensive emergencies.
The most common events reported during oral or intra-
venous therapy are dizziness, nausea and headache and
they are mild and transient and due to a too rapid decrease
in blood pressure.
The initial dose for hypertensive crises is a bolus of
12.5–50 mg as. A second 50 mg bolus can be administered
if no effect is observed within 5 min. Alternatively, a
continuous infusion of urapidil can be administered at an
initial rate of 2 mg/min and a maintenance infusion of
9 mg/h.
5.11 Clonidin
Clonidine, a central acting a2-agonist, is one of the most
frequently used drugs in hypertensive emergencies in
Europe [44].
When administered endovenously, 150–300 lg of
clonidine are given as slow bolus (10–15 min). Effect on
BP typically begins in 10 min and lasts for 13 h. Most
common side effects are bradycardia and atrioventricular
block. The pharmacokinetics of clonidine is dose-propor-
tional in the range of 100–600 lg.
When prescribing clonidine, physicians must take into
account two important aspects: risk of rebound hyperten-
sion and its sedative properties at high dose. Abrupt ces-
sation of clonidine may result in severe hypertensive crisis
that often will not respond to therapy without reinstitution
of the drug. Finally, clonidine acts as central nervous
system depressant, for this reason is useful in specific
setting as vegetative crisis after neurological events.
5.12 Phentolamine
Phentolamine, a competitive antagonist of peripheral a1-
and a2-receptors, is generally used to treat hypertensive
emergencies induced by catecholamine excess, such as
pheochromocytoma, interactions between monoamine
oxidase inhibitors and other drugs or food, cocaine toxicity,
amphetamine overdose, or clonidine withdrawal Phento-
lamine is given as an i.v. bolus dose of 5–15 mg every 5 to
15 min until the blood pressure is controlled. The onset of
action is 1–2 min. The half-life of phentolamine is
approximately 20 min, and its duration of action is \ 1 h.
It also can be given as a continuous infusion (0.2–0.5 mg/
min) for maintenance therapy. It should be used cautiously
in patients with CAD, as it can induce angina or MI.
Phentolamine use is commonly associated with reflex
tachycardia.
Tachycardia, flushing, and headache are also common
adverse effects. Compensatory tachycardia is managed
with an i.v. b-blocker [45].
Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room
6 Outcome and Subsequent Management
Data about the impact of hypertensive urgencies-emer-
gencies on the prognosis and on the occurrence of subse-
quent cardiovascular events are scanty and heterogeneous.
Collecting information about the outcome would be
important to direct management and to organize future
follow up of these patients.
Role of hypertensive urgencies as independent risk
factor for subsequent cardiovascular events is described in
only one prospective study. It collects data of consecutive
patients admitted to the ED with hypertensive urgency
during a 5-years-follow-up. These patients have a higher
rate of cardiovascular events (defined as acute coronary
syndrome, acute stroke, new-onset atrial fibrillation, acute
left ventricular failure and aortic aneurysm) during follow-
up compared with those without hypertensive urgency
(22.9 vs 14.2%; P = 0.005). Moreover, a regression anal-
ysis identifies age (P \ 0.001) and hypertensive urgency
(P = 0.035) as independent predictors for subsequent car-
diovascular events [46].
Further information comes from retrospective studies
and particularly from the analysis of the STAT (Studying
the Treatment of Acute hypertension) registry. This is a
25-institution US registry of consecutive patients with
acute severe hypertension treated with intravenous therapy
in a critical care setting with or without organ damage.
Previous analysis of these data allow to described a 6.9%
hospital mortality rate (higher in patients with intracranial
hemorrhage reaching the 20%) with a subsequent 90-day
mortality of 4.6% in hypertensive urgencies-emergencies.
While hospital mortality is higher in patients with organ
damage the same was not for post discharge mortality [3].
Clinical predictors of 90-day hospital readmission for
hypertension include: previous hospitalization for hyper-
tensive crisis, history of chronic kidney disease on dialysis,
drug abuse, seizures or dyspnea as presenting symptoms.
Among prognostic factors investigated, acute kidney
injury appears to be significantly associated with increased
risk of adverse cardiac events and death [8] while, evi-
dences are against a predictive role of troponin elevation
during the hypertensive urgencies-emergencies [48–50].
Finally other to studies give us important information
regarding management. Into the first one patients with
hypertensive urgency admitted to the emergency depart-
ment were compared to those managed in office setting. No
substantial benefit in outcome emerges, but visits to the
emergency department are associated with more hospital-
izations at 30-day follow up. At 6 months, there was no
difference in major cardiovascular events rate (0.9 percent
in both groups) neither in blood pressure control rate at
6 months [51].
Another retrospective study described the impact of
antihypertensive therapy on hypertensive urgencies in
emergency department. Of 1016 patients enrolled, 435
receive acute treatment for blood pressure control and 581
patients do not. Comparing the two groups, no difference
emerged in hospital readmission at 24 h (4.4 vs 2.4%;
p = ns) and at 30 days (18.9 vs 15.2%; p = ns) as well as in
30 days mortality (0.2 vs 0.2%; p = ns) and one year
mortality (2.1 vs 1.6%; p = ns) [52].
No guidelines reports on the subsequent management
and follow up after hypertensive urgencies-emergencies.
Despite this, the previous cited evidences suggest (indi-
rectly) that the most important prognostic factor after res-
olution of an hypertensive urgencies-emergencies is the
subsequent BP control [3, 46–48]. For these reason, some
general indications on patient management after hyper-
tensive urgencies-emergencies are widely accepted.
Since patients with hypertensive urgency are generally
managed in clinician’s office, subsequent management
should be also carried out in that setting. Also patients who
are referred to the emergency department, once excluded
presence of clinical conditions that require hospitalization,
should be addressed to office follow up. Increase in dose of
existing antihypertensive medications or add another agent
are generally required and, over the subsequent weeks and
months, dose and selection of medications should be tai-
lored to achieve the desired blood pressure goals.
7 Conclusions
Hypertensive urgencies-emergencies are important and
common events that need to be well known among who work
in the emergency department. Anamnestic information,
physical examination and instrumental evaluation determine
the following management that could need oral (for urgen-
cies) or intravenous (for emergencies) anti-hypertensives
drugs. The choice of the specific drugs depend on the
underlying causes of the crisis, patient’s demographics,
cardiovascular risk and comorbidities. Subsequent man-
agement with particular attention on chronic BP values
control is important as the right treatment of the acute phase.
Compliance with Ethical Standards
Funding This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest All the authors declares that they have no con-
flict of interest.

Ethical approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
standards.
Informed consent Informed consent was obtained from all individ-
ual participants included in the study.
References
1. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/
ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for
the prevention, detection, evaluation, and management of high
blood pressure in adults. J Am Coll Cardiol.
2017;71(19):e127–248.
2. Farias S, Peacock WF, Gonzalez M, Levy PD. Impact of initial
blood pressure on antihypertensive response in patients with
acute hypertension. Am J Emerg Med. 2014;32:833–6.
3. Katz JN, Gore JM, Amin A, et al. Practice patterns, outcomes,
and end-organ dysfunction for patients with acute severe hyper-
tension: the Studying the Treatment of Acute hyperTension
(STAT) Registry. Am Heart J. 2009;158:599–606.
4. Vilela Martin JF, Higashiama É, Garcia E, Luizon MR, Cipullo
JP. Hypertensive crisis profile. Prevalence and clinical presenta-
tion. Arq Bras Cardiol. 2004;83:125–36.
5. Zampaglione B, Pascale C, Marchisio M, Cavalo-Perin P.
Hypertensive urgencies and emergencies: prevalence and clinical
presentation. Hypertension. 1996;27:144–7.
6. Karras DJ, Kruus LK, Cienki JJ, et al. Evaluation and treatment
of patients with severely elevated blood pressure in academic
emergency departments: a multicenter study. Ann Emerg Med.
2006;47:230–6.
7. Donald G, Vidt MD. Emergency room management of hyper-
tensive urgencies and emergencies. J. Clin. Hypertens.
2000;3:158–64.
8. Marik PE, Varon J. Hypertensive crises: challenges and man-
agement. Chest. 2007;131:1949–62.
9. van den Born BJH, Beutler JJ, Gaillard CAJM, de Gooijer A, van
den Meiracker AH, Kroon AA. Dutch guideline for the man-
agement of hypertensive crisis—2010 revision. Neth J Med.
2011;69:248–55.
10. Muiesan M, Salvetti M, Amadoro V, di Somma S, Perlini S,
Semplicini A, Borghi C, Volpe M, Saba P, Cameli M, Ciccone M,
Maiello M, Modesti P. An update on hypertensive emergencies
and urgencies. J Cardiovasc Med. 2015;16:372–82.
11. Kaya A, Tatlisu MA, Kaplan Kaya T, et al. Sublingual vs. oral
captopril in hypertensive crisis. J Emerg Med. 2016;50:108–15.
12. Tartaglino B. In: Edizioni Medico Scientifiche, editors. Farmaci e
procedure in medicina d’urgenza. 2nd ed. 2007.
13. Cline DM. Tintinalli’s emergency medicine. In: American Col-
lege of Emergency Medicine, editors. A comprehensive study
guide, 8th ed. 2016.
14. Gemici K. A comparison of safety and efficacy of sublingual
captopril with sublingual nifedipine in hypertensive crisis. Int J
Angiol. 1999;8:147–9.
15. Moharamzad Y. Clinical efficacy of sublingual captopril in the
treatmentofhypertensiveurgency. Singapore Med J.
2009;50:400–2.
16. Damasceno A, Ferreira B, Patel S, Sevene EPJ. Efficacy of
captopril and nifedipine in black and white patients with hyper-
tensive crisis. J Hum Hypertens. 1997;11:471–6.
A. Maloberti et al.
17. Grossman E, Messerli FH, Grodzicky T, Kowey P. Should a
moratorium be placed on sublingual nifedipine capsules given for
hypertensive emergencies and pseudoemergencies. JAMA.
1996;276(16):1328–31.
18. Donnelly R, Meredith PA, Miller SHK, Howie CA, Elliott HL.
Pharmacodynarnic modeling of the antihypertensive response to
amlodipine. Clin Pharmacol Ther. 1993;54:303–10.
19. Varon J. Treatment of acute severe hypertension: current and
newer agents. Drugs. 2008;68:283–97.
20. Marx P, Reid D. Labetalol infusion in acute myocardial infarction
with systemic hypertension. Br J Clin Pharmacol. 1979;8:233S–
8S.
21. Olsen KS, Svendsen LB, Larsen FS, Paulson OB. Effect of
labetalol on cerebral blood flow, oxygen metabolism and
autoregulation in healthy humans. Br J Anaesth. 1995;75:51–4.
22. Hypertension IN in the T of PA. Intravenous nicardipine in the
treatment of postoperative arterial hypertension. J Cardiothorac
Vasc Anesth. 1997;11:160–4.
23. Nordlander M, Sjöquist PO, Ericsson HRL. Pharmacodynamic,
pharmacokinetic and clinical effects of clevidipine, an ultrashort-
acting calcium antagonist for rapid blood pressure control. Car-
diovasc Drug Rev. 2004;22:227–50.
24. Rodrı́guez G, Varon J. Clevidipine: a unique agent for the critical
care practitioner. Crit Care Shock. 2006;9:37–41.
25. Kw K. Clevidipine: an ultra short-acting calcium channel
antagonist for acute hypertension. Ann Pharmacother.
2009;43:1258–65.
26. Rivera A, Montoya E, Varon J. IBPC-6536-intravenous-clev-
idipine-butyrate-for-the-management-of-blood. Integr Blood
Press Control. 2010;3:105–11.
27. Tulman DB, Stawicki SPA, Papadimos TJ, Murphy CV, Bergese
SD. Advances in management of acute hypertension: a concise
review. Discov Med. 2012;13:375383.
28. Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials:
comparative studies of clevidipine to nitroglycerin, sodium
nitroprusside, and nicardipine for acute hypertension treatment in
cardiac surgery patients. Anesth Analg. 2008;107:1110–21.
29. Levy JH, Mancao MY, Gitter R, et al. Clevidipine effectively and
rapidly controls blood pressure preoperatively in cardiac surgery
patients: the results of the randomized, placebo-controlled effi-
cacy study of clevidipine assessing its preoperative antihyper-
tensive effect in cardiac surgery-1. Anesth Analg.
2007;105:918–25.
30. Singla N, Warltier DC, Gandhi SD, et al. Treatment of acute
postoperative hypertension in cardiac surgery patients: an effi-
cacy study of clevidipine assessing its postoperative antihyper-
tensive effect in cardiac surgery-2 (escape-2), a randomized,
double-blind, placebo-controlled trial. Anesth Analg.
2008;107:59–67.
31. Pollack CV, Varon J, Garrison NA, et al. Clevidipine, an intra-
venous dihydropyridine calcium channel blocker, is safe and
effective for treatment of patients with acute severe hypertension.
Ann Emerg Med. 2009;53:329–38.
32. Murphy MB, Murray CSG. Fenoldopam: a selective peripheral
dopamine-receptor agonist for the treatment of severe hyperten-
sion. N Engl J Med. 2001;345:1548–57.
33. White WB, Radford MJ, Gonzalez FM, Weed SG, McCabe EJ,
Katz AM. Selective dopamine-1 agonist therapy in severe
hypertension: effects of intravenous fenoldopam. J Am Coll
Cardiol. 1988;11:1118–23.
34. Khot UN, Novaro GM, Popović ZB, Mills RM, Thomas JD,
Tuzcu EM, Hammer D, Nissen SEFG. Nitroprusside in critically
ill patients with left ventricular dysfunction and aortic stenosis.
N Engl J Med. 2003;348:1756–63.
Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room
35. Kondo T, Brock MBH. Effect of intra-arterial sodium nitro-
prusside on intracranial pressure and cerebral autoregulation. Jpn
Heart J. 1984;25:231–7.
36. Mann T, Cohn PF, Holman LB, Green LH, Markis JE, Phillips
DA. Effect of nitroprusside on regional myocardial blood flow in
coronary artery disease. Results in 25 patients and comparison
with nitroglycerin. Circulation. 1978;57:732–8.
37. Niknahad HOP. Involvement of nitric oxide in nitroprusside-in-
duced hepatocyte cytotoxicity. Biochem Pharmacol.
1996;51:1031–9.
38. Pasch T, Schulz VHG. Nitroprusside-induced formation of cya-
nide and its detoxication with thiosulfate during deliberate
hypotension. J Cardiovasc Pharmacol. 1983;5:77–85.
39. Schulz V. Clinical pharmacokinetics of nitroprusside, cyanide,
thiosulphate and thiocyanate. Clin Pharmacokinet.
1984;9:239–51.
40. Ludden TM, Shepherd AMM, McNay JL, Lin MS. Hydralazine
kinetics in hypertensive patients after intravenous administration.
Clin Pharmacol Ther. 1980;28:736–42.
41. Buch J. Urapidil, a dual-acting antihypertensive agent: current
usage considerations. Adv Ther. 2010;27:426–43.
42. Alijotas-Reig J, Bove-Farre I, De Cabo-Frances F, Angles-Coll
R. Effectiveness and safety of prehospital urapidil for hyperten-
sive emergencies. Am J Emerg Med. 2001;19:130–3.
43. Grossman E, Ironi ANMF. Comparative tolerability profile of
hypertensive crisis treatments. Drug Saf. 1998;19:99–122.
44. Vuylsteke A, Vincent JL, Payen D, et al. Characteristics, practice
patterns, and outcomes in patients with acute hypertension:
European registry for studying the treatment of acute hyperten-
sion (Euro-STAT) registry. Crit Care. 2011;15:1–9.
45. Rhoney D, Peacock WF. Intravenous therapy for hypertensive
emergencies, part 1. Am J Heal Pharm. 2009;66:1343–52.
46. Vlcek M, Bur A, Woisetschlger C, Herkner H, Laggner AN,
Hirschl MM. Association between hypertensive urgencies and
subsequent cardiovascular events in patients with hypertension.
J Hypertens. 2008;26:657–62.
47. Gore JM, Peterson E, Amin A, et al. Predictors of 90-day read-
mission among patients with acute severe hypertension. The
cross-sectional observational Studying the Treatment of Acute
hyperTension (STAT) study. Am Heart J. 2010;160:3.
48. Afonso L, Bandaru H, Rathod A, Badheka A, Ali Kizilbash M,
Zmily H, Jacobsen G, Chattahi J, Mohamad T, Koneru J, Flack
JWD. Prevalence, determinants, and clinical significance of car-
diac troponin-I elevation in individuals admitted for a hyperten-
sive emergency. J Clin Hypertens. 2011;13:551–6.
49. Badheka A, Shenoy M, Rathod A, Tuliani T, Afonso L. Long-
term mortality and role of troponin elevation in hypertensive
emergencies. Am J Cardiol. 2012;109:600.
50. Szczech LA, Granger CB, Dasta JF, et al. Acute kidney injury
and cardiovascular outcomes in acute severe hypertension. Cir-
culation. 2010;121:2183–91.
51. Patel KK, Young L, Howell EH, et al. Characteristics and out-
comes of patients presenting with hypertensive urgency in the
office setting. JAMA Intern Med. 2016;176:981–8.
52. Levy PD, Mahn JJ, Miller J, et al. Blood pressure treatment and
outcomes in hypertensive patients without acute target organ
damage: a retrospective cohort. Am J Emerg Med.
2015;33:1219–24.